ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Towards Translation of PqsR Inverse Agonists: From In Vitro Efficacy Optimization to In Vivo Proof-of-Principle.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Management of Adult Bronchiectasis: Consensus-Based Guidelines of the German Respiratory Society.Respiration; international review of thoracic diseases · 2026Guideline
- A bibliometric analysis on discovering anti-quorum sensing agents against clinically relevant pathogens: current status, development, and future directions.Frontiers in microbiology · 2023Pooled it
- Multiparameter Optimization ofJournal of medicinal chemistry · 2026Article
- Chemical-mediated alteration of antibiotic susceptibility: mechanisms and potential new targets for antibiotic adjuvant discovery.Journal of bacteriology · 2026Review
- Exploiting Pharmacokinetic/Pharmacodynamic Methods for Optimizing and Accelerating Drug Development of Innovative Anti-Infectives.ChemMedChem · 2026Review
- Inhibitors of the PqsR Quorum-Sensing Receptor Reveal Differential Roles for PqsE and RhlI in Control of Phenazine Production.ACS chemical biology · 2025Article
- Domain adaptable language modeling of chemical compounds identifies potent pathoblockers for Pseudomonas aeruginosa.Communications chemistry · 2025Article
- From Bones to Bugs: Structure-Based Development of Raloxifene-Derived Pathoblockers That Inhibit Pyocyanin Production inJournal of medicinal chemistry · 2025Article
- Nanoparticles in liposomes: a platform for increased antibiotic selectivity in multidrug resistant bacteria in respiratory tract infections.Drug delivery and translational research · 2025Article
- Quorum Sensing and its Inhibition inCurrent drug targets · 2025Review
- Systematic bacteriophage selection for the lysis of multipleFrontiers in cellular and infection microbiology · 2025Article
- Antibiotic resistance and tolerance: What can drug delivery do against this global threat?Drug delivery and translational research · 2024Article
- Research Progress on the Combination of Quorum-Sensing Inhibitors and Antibiotics against Bacterial Resistance.Molecules (Basel, Switzerland) · 2024Review
- Enzyme-Linked Lipid Nanocarriers for Coping Pseudomonal Pulmonary Infection. Would Nanocarriers Complement Biofilm Disruption or Pave Its Road?International journal of nanomedicine · 2024Article
- Article
- Development of Quinazolinone Derivatives as Modulators of Virulence Factors ofMolecules (Basel, Switzerland) · 2023Article
- Towards Translation of PqsR Inverse Agonists: From In Vitro Efficacy Optimization to In Vivo Proof-of-Principle.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
Abstract
Pseudomonas aeruginosa (PA) is an opportunistic human pathogen, which is involved in a wide range of dangerous infections. It develops alarming resistances toward antibiotic treatment. Therefore, alternative strategies, which suppress pathogenicity or synergize with antibiotic treatments are in great need to combat these infections more effectively. One promising approach is to disarm the bacteria by interfering with their quorum sensing (QS) system, which regulates the release of various virulence factors as well as biofilm formation. Herein, this work reports the rational design, optimization, and in-depth profiling of a new class of Pseudomonas quinolone signaling receptor (PqsR) inverse agonists. The resulting frontrunner compound features a pyrimidine-based scaffold, high in vitro and in vivo efficacy, favorable pharmacokinetics as well as clean safety pharmacology characteristics, which provide the basis for potential pulmonary as well as systemic routes of administration. An X-ray crystal structure in complex with PqsR facilitated further structure-guided lead optimization. The compound demonstrates potent pyocyanin suppression, synergizes with aminoglycoside antibiotic tobramycin against PA biofilms, and is active against a panel of clinical isolates from bronchiectasis patients. Importantly, this in vitro effect translated into in vivo efficacy in a neutropenic thigh infection model in mice providing a proof-of-principle for adjunctive treatment scenarios.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.